Fructan containing composition for the prevention and treatment of colon cancer and method for the prevention and treatment of same

ABSTRACT

The use is provided of a fructran with an average degree of polymerisation of at least 15 for the manufacture of a composition for the prevention and/or treatment of colon cancer in non-bovine mammals, particularly in human beings.  
     Also provided is a method of prevention and treatment of colon cancer in a non-bovine mammal, particularly in a human being, comprising administering to said mammal a composition comprising an effective dose of a fructan with an average degree of polymerisation of at least 15.  
     The said composition can be a medicament as well as a functional food. In a preferred embodiment the fructan is inulin, more preferably inulin with an average degree of polymerisation of at least 20.

FIELD OF THE INVENTION

[0001] The present invention relates to the use of certain fructans,preferably certain inulins, for the manufacture of a composition for theprevention and/or treatment of colon cancer in non-bovine mammals.

[0002] The present invention also relates to the use of compositionscomprising certain fructans, preferably certain inulins, for theprevention and/or treatment of colon cancer in non-bovine mammals, andto a method of prevention and/or treatment of colon cancer in non-bovinemammals.

BACKGROUND OF THE INVENTION

[0003] Cancer in mammals is a disease which is already known fromAncient Times. Nowadavs cancer, particularly lung, breast and coloncancer, has become one of the major causes of death of non-bovinemammals, in particular of humans, in the industrialised world.

[0004] The cancer disease is known to proceed in several steps,including genesis of cells of modified genome and functionalityresulting in the formation of malignant cells; uncontrolled localproliferation of the malignant cells and invasion of adjacent normalbody structures; and metastasis. During metastasis malignant cells arespread in a body cavity and/or throughout the body via the blood streamand/or the lymph, with invasion of various normal body structures. Theinvasion of the normal body structures results in their malfunctioningand/or destruction, eventually leading to the death of the affectedmammal.

[0005] Various factors which can provoke carcinogenesis and cancer havealready been identified, including certain viral infections, exposure toionising radiation, exposure to certain mineral fibres, exposure tochemical mutagens, and improper diet.

[0006] As a result thereof various preventive measures have beenintroduced which have shown to be successful in preventing or reducingthe occurrence of certain cancers.

[0007] Furthermore, various surgical and chemotherapeutical methods havebeen developed for the treatment of cancer. According to the type ofcancer, the stage of the disease and the particulars of the affectedmammal, these methods have been shown effective to a more or lesserdegree.

[0008] Many reliable animal models for the study of the genesis andevolution of various cancers are available at present, enabling theevaluation of the preventive and curative properties of miscellaneouschemicals and dietary products.

[0009] Epidemiological studies in combination with studies on animalmodels have lead to the identification of dietary fibres as an importantfactor in the prevention and inhibition of certain cancers in mammals.

[0010] Dietary fibres are commonly defined as components of plant cellswhich are resistant to hydrolysis by the alimentary enzymes of man.Dietary fibres comprise cellulose, hemicellulose, polysaccharides,pectin, gums, waxes and lignin. According to this definition, fructans,which are soluble and edible polysaccharides, are dietary fibres.Fructans are composed of chains of carbohydrates which consist mostly offructose units and in which fructosyl-fructose linkages constitute themajority of the linkages. Fructans commonly occur as polydispersecarbohydrates. They occur in plants, but they also can originate frombacterial activity and they can be synthesised enzymatically as well.All these fructans present typical dietary fibre properties; they areembraced by the present invention and are referred to herein asfructan(s).

[0011] Fructans are well known compounds including levan and inulincarbohydrates. Levans are D-fructans generally consisting of chains offructose units which are essentially connected to each other by β(2-6)linkages. Inulins are also D-fructans generally consisting of chains offructose units but which are essentially connected to each other byβ(2-1) linkages. Most of the inulin chains terminate in one glucoseunit.

[0012] Levans may occur as linear chain carbohydrates but they aremostly composed of branched fructose chains, whereas inulins aregenerally composed of linear chain carbohydrates but they may also occuras chains of fructose units which are branched to a larger or lesserextent. Levans and inulins which are suitable according to the presentinvention include linear and branched chain carbohydrates, as well asmixtures of said linear and branched chain carbohydrates.

[0013] Inulins occur in many plants and crops and can occur atconcentrations of about 10 to 20% on fresh weight in chicory, dahliatubers and Jerusalem artichoke. They can be isolated from these plants,purified, and optionally refined to remove impurities and undesiredfractions of carbohydrates, at industrial scale, according to well knowntechniques.

[0014] Inulins can be represented by the general formulae GFn and Fmwherein G represents a glucose unit, F represents a fructose unit, nrepresents the number of fructose units linked to the terminal glucoseunit, and m represents the number of fructose units linked to each otherin the carbohydrate chain. The number of saccharide units (fructose andglucose units) in one fructan molecule, i.e. the values n+1 and m in theabove formulae, are commonly referred to as the degree of polymerisationand represented as (DP). Often the parameter average degree ofpolymerisation ({overscore (DP)}) is used too, which is the valuecorresponding to the total number of saccharide units divided by thetotal number of saccharide molecules present in a given (poly)saccharidecomposition.

[0015] Inulin from plant origin is a polydisperse composition offructose chains with a degree of polymerisation (DP) ranging from 2 toabout 100, whereas inulin from bacterial origin usually has a higherdegree of polymerisation.

[0016] Fructans, including inulins of general formulae GFn and Fm, witha lower degree of polymerisation, usually defined as a (DP) <10, arecommonly named oligofructoses and are referred to herein accordingly.

[0017] Inulin is commercially available. For example, inulin fromchicory is available as RAFTILINE® from ORAFTI, (Tienen, Belgium), invarious grades. Typical RAFTILINE® grades are, for example, ST, ST-Geland GR (which have an average degree of polymerisation ({overscore(DP)}) of 10 and contain in total about 8% by weight glucose, fructoseand sucrose), LS (which has also an average degree of polymerisation of10 but which contains in total less than 1% by weight glucose, fructoseand sucrose), and HP (high performance inulin) and HP-Gel (which have anaverage degree of polymerisation of ≧23, commonly about 25, and areessentially free of glucose, fructose and sucrose).

[0018] Oligofructoses are usually obtained by partial, acidic orenzymatic hydrolysis of inulins and can also be obtained by enzymaticsynthesis from sucrose, according to techniques which are well-known inthe art. Oligofructoses are commercially available. Several grades ofoligofructose are, for example, available from ORAFTI, (Tienen,Belgium), as RAFTILOSE®, e.g. RAFTILOSE® P95 which contains about 95% byweight oligofructoses with a degree of polymerisation ranging from 2 to7 and about 5% by weight in total of glucose, fructose and sucrose.

STATE OF THE ART

[0019] Dietary fibres, in particular fructans, are known to have effectson various physiological functions and mechanisms in mammals.

[0020] In non-bovine mammals, these fibres are almost not metabolised inthe mouth, the stomach and the small intestine, and they thus almostquantitatively enter the large intestine where they are completelyfermented by the colonic microflora. This phenomenon results in variousbeneficial health effects in non-bovine mammals such as, for example, areduction of the intestinal transit time, a decrease of the intestinalpH, a bifidus stimulating activity in the colon, an increase of thestool weight (bulking) and stool frequency.

[0021] Fructans, particularly inulin, are also known to have abeneficial effect on lipid metabolism, including a lowering effect onblood cholesterol and on serum triglycerides, and an increasing effecton the HDL/LDL ratio.

[0022] P. D. Cooper et al., Molecul. Immunol., 23 (8), 895, (1986),describe the activation of the alternative pathway of complement bygamma-inulin (a specific polymorphic form of dahlia inulin), and it isknown that an activator of the alternative pathway of complement canhave a potential non-specific anti-tumour effect.

[0023] Furthermore, fructans, particularly inulin, are described to havepotential in the prevention and inhibition of cancer.

[0024] P. D. Cooper et al., (Molecul. Immunol., 23 (8), 903, (1986) havedemonstrated that intraperitoneally injected gamma-inulin can prolongthe survival of melanoma bearing mice.

[0025] It has also been disclosed that cultures of bifidobacteriainhibit 2-amino-3-methyl-imidazol[4,5-f]quinoline induced colon, liver,and mammary carcinogenesis (B.S. Reddy et al., Cancer Res., 53,3914-3918, (1993) and azoxymethane-induced colon carcinogenesis (N.Kulkarni et al., Proc. Soc. Exptl. Biol. Med., 207, 278-283, (1994) inrats.

[0026] European patent application EP 0 692 252 A1 discloses thesuppressing effect of the oligofructose RAFTILOSE® P95 (ex ORAFTI,Belgium; consisting of 95% of oligofructose chains with a degree ofpolymerisation (DP) between 2 and 7) and of the inulins RAFTILINE® ST,GR and LS, (defined hereinbefore and having an average degree ofpolymerisation of about 10) on breast carcinogenesis induced byinjection of N-methylnitrosourea (MNU) in rats as well as on the growthof the transplantable TLT tumour (Taper Liver Tumour) in mice. Theinvestigated oligofructose and inulins showed to have about equalcarcinogenesis protective and cancer inhibiting effects.

[0027] Furthermore, the relation between the intake of dietary fibresand the reduction of the risk of colon cancer has been disclosed inseveral publications, e.g. J. Potter et al., Principles ofChemoprevention, IARC Scientific Publication N°139, 61-90, (1996); G. R.Howe et al., J. Natl. Cancer Inst., 84, 1887-1896, (1992); and B. S.Reddy et al., Gastoenterol., 102, 1475-1482, (1992).

[0028] However, in spite of the enormous efforts already made in thefight against cancer diseases, and colon cancer in particular, theprevention and successful inhibition and curing of colon cancer is notalways possible yet. Therefore, Medicine is still looking for improvingthe prevention, inhibition and curing of colon cancer. For variousreasons such as the patient's comfort, chemotherapeutical methods aremost preferred. Accordingly, there is a continuously ongoing search forimproved and/or alternative compositions and therapeutical methodspresenting a beneficial effect with respect to the inhibition and/ortreatment of colon cancer, and /or presenting less undesirable sideeffects compared to known compositions and therapeutical methods.

DESCRIPTION OF THE INVENTION

[0029] The applicant is providing by the present invention a solution toone or more of the above mentioned problems, which even may presentadditional advantages.

[0030] By the term colon cancer is meant herein the colon cancer diseasein any of its steps, including colon carcinogenesis, the formation ofmalignant cells in the colon, proliferation of said malignant cells andformation of tumours in the colon and /or invasion of normal colonstructures by said malignant cells.

[0031] The invention is based on the findings made by the inventorsduring extensive studies that fructans with a higher degree ofpolymerisation, in particular fructans having an average degree ofpolymerisation of 15 or higher, present improved preventive andinhibiting properties against colon cancer in non-bovine mammalscompared to fructans with a lower degree of polymerisation.

[0032] In view of the prior art, it could be expected that fructans witha higher degree of polymerisation, could, as do certain fructans with alower degree of polymerisation, have preventive and/or inhibitiveproperties against colon cancer. However, the surprising findings of theinventors that fructans, in particular inulins, with a higher averagedegree of polymerisation, present significantly enhanced preventive andinhibiting properties against colon cancer in non-bovine mammals,compared to fructans with a lower average degree of polymerisation,could not be expected at all having regard to the state of the art.

[0033] Accordingly, in one aspect, the present invention relates to theuse of a fructan with an average degree of polymerisation of at least 15for the manufacture of a composition for the prevention and/or treatmentof colon cancer in non-bovine mammals, particularly in human beings.

[0034] In another aspect, the invention relates to the use of acomposition comprising a fructan with an average degree ofpolymerisation of at least 15, for the prevention and/or treatment ofcolon cancer in non-bovine mammals, particularly human beings.

[0035] In a further aspect, the invention relates to a method for theprevention and/or treatment of colon cancer in non-bovine mammals,particularly human beings, by administering to said mammal susceptibleof colon cancer, in need of such prevention or treatment, a compositioncomprising an effective dose of a fructan with an average degree ofpolymerisation of at least 15.

[0036] In one preferred embodiment, the fructan is levan, preferablywith an average degree of polymerisation of at least 20, more preferablyranging from 20 to 50.

[0037] In another preferred embodiment, the fructan is inulin,preferably with an average degree of polymerisation of at least 20, evenmore preferably ranging from 20 to 70. In a further preferredembodiment, the inulin has an average degree of polymerisation rangingfrom 20 to 40. A typically preferred inulin has an average degree ofpolymerisation about 25.

[0038] Inulin essentially consisting of linear polysaccharide chains orinulin containing up to about 2%, by weight branched polysaccharidechains, are suitable according to the invention, but inulin containing ahigher percentage of branched chains and even inulin essentiallyconsisting of branched polysaccharide chains, and even mixtures of saidlinear and branched inulins, are suitable as well according to theinvention. Typical inulins suitable according to the present inventionare chicory inulins, for example RAFTILINE® HP and RAFTILINE® HP-Gel(both high performance inulins [in short HP inulin] ex ORAFTI, Belgium),with an average degree of polymerisation of about 25.

[0039] By the term composition according to the present invention ismeant herein a medicament, (i.e. a composition which has a prophylacticand/or a curative effect on a mammal to which it has been administered),as well as a functional food, (i.e. a food product for human beings orfor a non-human mammal, containing an additional functional ingredient,and which apart from its nutritional properties, additionally providesto that being one or more beneficial physiological effects). In thefunctional food compositions according to the present invention, saidadditional functional ingredient is meant to be a fructan, includinglevans and inulins, as defined herein before. Typical beneficialphysiological effects are, for example, beneficial effects on thedigestive tract, effects on lipid metabolism and preventive effectsagainst cancer, in particular colon cancer.

[0040] When, in accordance with the present invention, the compositionis a medicament, it can consist of the defined fructan or it cancomprise said fructan in combination with any pharmaceuticallyacceptable carrier, and optionally also in combination with one or morephysiologically active compounds, drugs or prodrugs. Said medicament canhave any form known in the art, and can be administered according toknown methods. Preferably, the medicament is in the form of a powder, atablet, a soft gel capsule, a syrup, a solution or a suspension, and isadministered orally. However, when present in an appropriate galenicform, the composition can also be administered parenterally, via tubefeeding or rectally.

[0041] When the composition according to the present invention is afunctional food, it is orally administered and it can be present in anyknown food form, such as, for example, a table spread, a dairy productsuch as e.g. a milk, a dairy dessert, a yoghurt, or a cheese, analcoholic or non-alcoholic drink, a bakery product, a chocolate, an icecream, a meat product, a fruit preparation, a confectionery product, acereal product, a sauce, a soup, a snack, a dry mix, a meal replacer, apet food, and the like.

[0042] The daily dosis effective in providing prevention against coloncancer preferably ranges, depending from the mammal species and thefructan species, from 0.01 to 2 g/kg body weight, more preferably from0.05 to 0.5 g/kg body weight.

[0043] The daily dosis effective in providing an inhibitive and/orcuring effect on colon cancer preferably ranges, depending from themammal species, the fructan species and the stage of development of thecolon cancer, from 0.2 to 3 g/kg body weight, more preferably from 0.5to 1.5 g/kg body weight.

[0044] In the method of prevention and/or treatment, includinginhibition and/or curing, of colon cancer in non-bovine mammals,preferably human beings, the daily dose of the composition according tothe present invention described hereinbefore, can be administered to asaid mammal susceptible of colon cancer and in need for such treatment,according to known methods in one or more unit doses during a shorter orlonger period of time, in function of strength of the effect provided bythe composition. When the composition is a functional food and apreventive effect is aimed at, the functional food is advantageouslyadministered in one or more forms over a longer period of time, mostpreferably during the whole lifetime of the mammal.

[0045] Besides the improved physiological, prophylactic and/ortherapeutical effects of the fructans with a higher degree ofpolymerisation compared to fructans with a lower degree ofpolymerisation, the compositions and method of treatment according tothe present invention present significantly additional advantages. Thecompositions, for example, are easy to take in or to administer, and themethod of treatment is easy to apply, without significant discomfort forthe concerned mammal. Furthermore, the presence of fructan chains with ahigher degree of polymerisation reduces certain discomforts oftenencountered with the intake of non-digestible carbohydrates such as e.g.soft stools, diarrhea, flatulence, bloating and intestinal cramps.

[0046] A further considerable advantage presented by the fructans, inparticular the preferred chicory inulin, relating to the presentinvention, is that they are naturally occurring, biodegradable productswhich are deprived of toxic effects and that they can be taken in andadministered to newborn as well as adult, including pregnant, and agedmammals. Compared to many known chemotherapeutical compositions, theintake of, administration of, and the treatment with a compositioncomprising the above defined fructans according to the presentinvention, is usually very well supported by the mammal and does notprovoke significant undesirable side effects or a significantdiscomfort, if any at all, to the mammal. Furthermore, the fructanssuitable according to the present invention are largely commerciallyavailable at acceptable cost.

[0047] Experimental Part

[0048] In support of the present invention, the following illustrativeexperimental data are given regarding a study made to determine theeffect of oligofructose and HP inulin on carcinogen-induced colonicaberrant crypt foci (ACF) formation in rat.

[0049] Aberrant crypt foci (ACF), which are recognized as earlypreneoplastic lesions in the colon, have consistently been observed inexperimentally induced colon carcinogenesis in laboratory animals(McLellan, E. A. et al., Cancer Res., 51, 5270-5274, (1991) andWargovich, M. H., et al., Cancer Epidemiol Biomarkers & Prev., 5,355-360, (1996)). Pretlow, T. P., et al., J. Cell. Biochem., 16G(Suppl.), 55-62, (1992), have also shown that these lesions are presentin the colonic mucosa of patients with colon cancer and have suggestedthat aberrant crypts are putative precursor lesions from which adenomasand carcinomas may develop in the colon. ACF express mutations in theapc gene and ras oncogene that appear to be biomarkers of colon cancerdevelopment (Vivona, A. A., et al., Carcinogenesis (Lond.) 14,1777-1781, (1993)).

[0050] There is some evidence that several inhibitors of ACF formationreduce the incidence of colon tumors in laboratory animals ( Wargovich,M. H., et al., Cancer Epidemiol Biomarkers & Prev., 5, 355-360, (1996)), suggesting that ACF induction can be used to evaluate novel agentsfor their potential chemopreventive properties against colon cancer.

[0051] Materials and Methods

[0052] Animals, diets, carcinogen, and chemopreventive agents.

[0053] Azoxymethane (AOM) was obtained from Ash Stevens (Detroit, Mich.,USA). RAFTILOSE® P95 and RAFTILINE® HP which contained on dry mattermainly oligofructose (95%) and inulin (99.5%), respectively, wereobtained from ORAFTI (Tienen, Belgium). RAFTILOSE® which was produced bypartial enzymatic hydrolysis of chicory inulin is a polydisperse β[2-1]fructan with a (DP) ranging between 2 and 7 and a ({overscore (DP)}) of4.5. RAFTILINE® HP (i.e. high performance inulin and abbreviated hereinto HP inulin) is chicory inulin of which the lower (DP) fraction hasbeen removed. Its (DP) ranges between 10 and 60 and it has a ({overscore(DP)}) of 25. This choice of test substrates thus allows to observeeffects of the degree of polymerisation.

[0054] Weanling male F344 rats were obtained from Charles River BreedingLaboratories (Kingston, N.Y., USA). All ingredients of the AIN-76Asemipurified diet were obtained from Dyets Inc., (Bethlehem, Pa., USA)and were stored at 4° C. until the experimental diets were prepared. Thepercentage composition of semipurified diet is as follows: casein, 20;D,L-methionine, 0.3; corn starch, 52; dextrose, 13; corn oil, 5;alphacel, 5; mineral mix (AIN-76A), 3.5; vitamin mix (AIN-76A), 1; andcholine bitartrate, 0.2 (Reddy B.S., et al., Cancer Res., 48, 6642-6647,(1988). The rats were held in quarantine for 1 week and had access tomodified AIN-76A semipurified control diet. They were randomlydistributed by weight into various dietary groups and were transferredto an animal holding room where they were housed in plastic cages, threerats/cage, under controlled conditions of a 12 h light/ 12 h dark cycle,50% relative humidity, and 21° C. room temperature. RAFTILOSE® andRAFTILINE® were added to the control diet at 10% level at the expense ofstarch.

[0055] Experimental procedure. Beginning at 5 weeks of age, groups ofanimals were fed the control or experimental diets. All animals exceptthe vehicle-treated rats received AOM s.c. once weekly at 7 and 8 weeksof age at a dose rate of 15 mg/kg body weight/week. Animals intended forvehicle treatment were given an equal volume of normal saline. The ratswere continued on control or experimental diets until the termination ofthe study, when they were 16 weeks of age. All animals were sacrificedby CO₂ euthanasia. The colons were removed, flushed with Krebs-Ringersolution, opened from cecum to anus, and fixed flat between two piecesof filter paper in 10% buffered formalin. After a minimum of 24 h inbuffered formalin, the colons were cut into 2-cm segments, placed in aPetri dish containing 0.2% methylene blue in Krebs-Ringer solution andkept for 5-10 min. They were then placed, mucosal side up, on amicroscope slide and observed through a light microscope. ACF wererecorded according to standard procedures (McLellan E. A., et al.,Cancer Res., 51, 5270-5274, (1991). Aberrant crypts were distinguishedfrom the surrounding normal crypts by their increased size,significantly increased distance from lamina to basal surface of cells,and the easily discernible pericryptal zone. Crypt multiplicity wasdetermined as the number of crypts in each focus and categorised asthose containing up to three, or four or more aberrant crypts/focus. Allcolons were scored by one observer without knowing the identity ofagents under study; scores were checked at random by a second observer.

[0056] Statistical Analysis. All results were expressed as the means ±SDand were analysed by one-tailed Student's t-test. Differences wereconsidered statistically significant at p<0.05.

[0057] Results

[0058] General Observations. The body weights of AOM-and vehicle-treatedanimals fed the control and experimental diets containing 10% inulin oroligofructose were comparable throughout the study (Table 1, hereafter).There were no signs of any adverse effects in liver, kidney, stomach,intestine or lungs of animals fed inulin or oligofructose.

[0059] Aberrant Crypt Foci. Table 2 hereafter summarises the AOM-inducedACF in the colon of rats fed the control and experimental diets. Theanimals administered saline (vehicle) and fed the control andexperimentals diets containing inulin or oligofructose showed noevidence of ACF formation in the colon (data not shown). In the animalsfed the control diet, AOM treatment induced on the average about 120ACF/colon. ACF were predominantly observed in the distal colons.Efficacy end points used in this study were inhibition of the totalnumber of ACF/colon as well as the reduction of the number of multicryptclusters (2 or more) of aberrant crypts/focus. Administration ofoligofructose or HP inulin in the diet significantly suppressed thetotal number of ACF/colon as compared to the control diet; the degree ofinhibition was significantly more pronounced in the animals fed HPinulin (p<0.006) than in those fed oligofructose (p<0.02). Cryptmultiplicity in terms of 2 or 3 aberrant crypts/focus was alsosignificantly inhibited in animals fed HP inulin (p<0.02-0.0001) oroligofructose (p<0.04-0.01).

[0060] Because multiplicity of aberrant crypts has been a probablepredictor of colon tumor outcome (Pretlow, T. P., et al., Carcinogenesis(Lond.), 13. 1509-1512, (1992) ), the present study used this criterionto evaluate oligofructose and HP inulin for their potential inhibitoryproperties.

[0061] The results of the present study indicate that orally takenoligofructose and HP inulin inhibits AOM-induced colonic ACF formationin rats supporting the potential colon tumor inhibitory properties ofchicory fructans. The experimental results clearly demonstrate that thepreventive and ACF inhibitory properties provided by a fructan (in casuHP inulin ) with a higher average degree of polymerisation, areconsiderably enhanced compared to a fructan (oligofructose) with a loweraverage degree of polymerisation. TABLE 1 Body weights of animals fedthe control diet and experimental diets containing oligofructose and HPinulin. Body weights (grams) on control and experimental diets at weekExperimental groups 0 3 6 10 AOM-treated 1. Control diet  119 ± 5.9^(a)173 ± 9.1 257 ± 11 320 ± 14 2. Oligofructose, 10% 119 ± 6.6 167 ± 9.8258 ± 15 327 ± 16 3. HP Inulin, 10% 120 ± 7.1  73 ± 7.8 259 ± 12 328 ±15 Saline-treated 4. Control diet 117 ± 8.5 179 ± 9.7 256 ± 9.8 329 ± 125. Oligofructose, 10% 120 ± 5.9 175 ± 7.3 264 ± 9.3 338 ± 12 6. HPInulin, 10% 119 ± 5.7 171 ± 6.0 256 ± 8.1 329 ± 13

[0062] TABLE 2 Effect of dietary oligofructose and HP inulin on colonicACF formation in male F344 rats. Foci containing number of aberrantcrypts Experimental 4 or more groups Total ACF /colon 1 crypt/focus 2crypts/focus 3 crypts/focus crypts/focus Control diet 120 ± 28 19.5 ±7.3 43.7 ± 7.8 28.2 ± 7.5 28.3 ± 8.2 Oligofructose, 10%  92 ± 28^(b)15.4 ± 7.5 31.2 ± 13^(b) 21.3 ± 7.8^(b) 23.9 ± 8.2 (p < 0.O24) (p <0.01) (p < 0.04) HP Inulin, 10%  78 ± 37^(b) 15.7 ± 8.2 24 ± 12^(b) 16.6± 7.2^(b) 21.8 ± 14.2 (p < 0.006) (p < 0.0001) (p < 0.02)

1. Use of a fructan with an average degree of polymerisation of at least15 for the manufacture of a composition for the prevention and/ortreatment of colon cancer in non-bovine mammals.
 2. Use according toclaim 1 wherein the mammal is selected from the group consisting of ahuman being, a dog and a cat.
 3. Use according to any of claims 1 or 2wherein the fructan is a levan.
 4. Use according to claim 3 wherein thelevan has an average degree of polymerisation of at least
 20. 5. Useaccording to any of claims 1 or 2 wherein the fructan is an inulin. 6.Use according to claim 5 wherein the inulin has an average degree ofpolymerisation of at least
 20. 7. Use according to claim 6 wherein theinulin has an average degree of polymerisation ranging from 20 to
 40. 8.Use according to any of daims 1 to 7 wherein the composition is amedicament.
 9. Use according to claim 8 wherein the medicament comprisessaid fructan in combination with a pharmaceutically acceptable carrierand optionally with a physiologically active compound, a drug or a prodrug.
 10. Use according to any of claims 1 to 7 wherein the compositionis a functional food.
 11. Use of a composition as defined in any ofclaims 1 to 10 for the prevention and/or treatment of colon cancer in anon-bovine mammal.
 12. Method of prevention of colon cancer in anon-bovine mammal comprising administering to said mammal susceptible ofcolon cancer in need of such treatment, a composition comprising aneffective dose of a fructan with an average degree of polymerisation ofat least
 15. 13. Method according to claim 12 wherein the daily dose offructan administered in one or more unit doses, ranges from 0.01 to 2g/kg body weight.
 14. Method of treatment of colon cancer in anon-bovine mammal comprising administering to said mammal in need ofsuch treatment, a composition comprising an effective dose of a fructanwith an average degree of polymerisation of at least
 15. 15. Methodaccording to claim 14 wherein the daily dose of fructan administered inone or more unit doses, ranges from 0.2 to 3 g/kg body weight. 16.Method according to any of claims 12, 13, 14 or 15 wherein the mammal isselected from the group consisting of a human being, a dog and a cat.17. Method according to claim 16, wherein the fructan is a levan. 18.Method according to claim 16 wherein the fructan is an inulin. 19.Method according to claim 18 wherein the inulin has an average degree ofpolymerisation of at least
 20. 20. Method according to claim 19 whereinthe inulin has an average degree of polymerisation ranging from 20 to60.
 21. Method according to any of claims 12 to 20 wherein thecomposition is a functional food.
 22. Method according to any of claims12 to 20 wherein the composition is a medicament.